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By dosage, the mean changes were: 500 mcg: 127% 750 mcg: 176% (single study) 1,000 mcg: 280% 1,500 mcg: 310% 2000 mcg: 260% 5,000 mcg: 62% While 1,500 mcg of vitamin B12 showed the highest average increase, the effect plateaued or declined at higher doses, suggesting a possible saturation of absorption pathways

Also, individuals with COMT defects can be at higher risk for accumulating too much peroxynitrites which builds up in their bodies, causing stiffness and muscle pain or brain fog and cardiovascular problems